期刊
EXPERIMENTAL NEUROLOGY
卷 233, 期 1, 页码 145-153出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2011.08.027
关键词
Parkinson's disease; Deep brain stimulation; Subthalamic nucleus; Depression; 5-HT; Microdialysis; In vivo electrophysiology
资金
- Parkinson's UK
- Netherlands Organization for Scientific Research
- Dutch Brain Foundation (Hersenstichting Nederland)
- Parkinson"
- s UK [G-0716] Funding Source: researchfish
Movement disability in advanced Parkinson's disease (PD) can be treated by high frequency stimulation (HFS) of the subthalamic nucleus (STN) but some patients experience psychiatric side-effects including depression, which is strongly linked to decreases in 5-hydroxytryptamine (5-HT). The current study investigated the effect of bilateral STN HFS on extracellular 5-HT in brain regions of anesthetized and freely moving rats as measured with microdialysis. Parallel in vivo electrophysiological experiments allowed a correlation of changes in extracellular 5-HT with the firing of 5-HT neurons. Bilateral STN HFS decreased (by up to 25%) extracellular levels of 5-HT in both striatum and medial prefrontal cortex of anesthetized rats. STN HFS also decreased extracellular 5-HT in the medial prefrontal cortex of freely moving rats. This decrease in extracellular 5-HT persisted after turning off the stimulation, and was present in dopamine-denervated rats. As with changes in extracellular 5-HT, in anesthetized rats STN HFS evoked a decrease in the in vivo firing of midbrain raphe 5-HT neurons that also persisted after cessation of stimulation. These data provide neurochemical evidence for an inhibition of 5-HT neurotransmission by STN HFS, which may contribute to its psychiatric side effects and guide therapeutic options. Crown Copyright (C) 2011 Published by Elsevier Inc. All rights reserved.
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